System for Blood Separation with Shielded Extraction Port and Optical Control

ABSTRACT

A centrifugal blood separation system comprising a rotor, a light source, an optical sensor, a control system, a separation vessel, and an optical cell on the separation vessel. The optical cell has a first extraction port extending radially outwardly into the optical cell, a red blood cell extraction port downstream from the first extraction port and extending into the optical cell beyond the first extraction port; and a dam between said first extraction port and said red blood cell extraction port, having an upper edge and a lower edge, wherein the first extraction port and the red cell extraction port are radially between the upper edge and the lower edge of the dam. Also, a first extraction port having a bore having a first diameter, a lumen having a second diameter smaller than the first diameter, and a frustro-conical passageway coupling the bore to the lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to U.S. Pat. No. 7,605,388, which isincorporated herein by reference. This application claims the priorityof U.S. Provisional Application No. 61/285,597, currently pending, filedon Dec. 11, 2009.

BACKGROUND OF INVENTION

Blood collection and processing play important roles in the worldwidehealth care system. In conventional large scale blood collection, bloodis removed from a donor or patient, separated into its various bloodcomponents via centrifugation, filtration, or elutriation and stored insterile containers for future infusion into a patient for therapeuticuse. The separated blood components typically include fractionscomprising red blood cells, white blood cells, platelets, and plasma.Separation of blood into its components can be performed continuouslyduring collection or can be performed subsequent to collection inbatches, particularly with respect to the processing of whole bloodsamples. Separation of blood into its various components under highlysterile conditions is critical to many therapeutic applications.

Recently, apheresis blood collection techniques have been adopted inmany large scale blood collection centers wherein a selected componentof blood is collected and the balance of the blood is returned to thedonor during collection. In apheresis, blood is removed from a donor andimmediately separated into its components by on-line blood processingmethods. Typically, on-line blood processing is provided by densitycentrifugation, filtration, or diffusion-based separation techniques.One or more of the separated blood components are collected and storedin sterile containers, while the remaining blood components are directlyre-circulated to the donor. An advantage of this method is that itallows more frequent donation from an individual donor because only aselected blood component is collected and purified. For example, a donorundergoing plateletpheresis, whereby platelets are collected and thenon-platelet blood components are returned to the donor, may donateblood as often as once every fourteen days.

Apheresis blood processing also plays an important role in a largenumber of therapeutic procedures. In these methods, blood is withdrawnfrom a patient undergoing therapy, separated, and a selected fraction iscollected while the remainder is returned to the patient. For example, apatient may undergo leukapheresis prior to radiation therapy, wherebythe white blood cell component of his blood is separated, collected andstored to avoid exposure to radiation.

Both conventional blood collection and apheresis systems typicallyemploy differential centrifugation methods for separating blood into itsvarious blood components. In differential centrifugation, blood iscirculated through a sterile separation chamber which is rotated at highrotational speeds about a central rotation axis. Rotation of theseparation chamber creates a centrifugal force directed along rotatingaxes of separation oriented perpendicular to the central rotation axisof the centrifuge. The centrifugal force generated upon rotationseparates particles suspended in the blood sample into discretefractions having different densities. Specifically, a blood sampleseparates into discrete phases corresponding to a higher densityfraction comprising red blood cells and a lower density fractioncomprising plasma. In addition, an intermediate density fractioncomprising platelets and leukocytes forms an interface layer between thered blood cells and the plasma. Descriptions of blood centrifugationdevices are provided in U.S. Pat. No. 5,653,887 and U.S. Pat. No.7,033,512.

To achieve continuous, high throughput blood separation, extraction orcollect ports are provided in most separation chambers. Extraction portsare capable of withdrawing material from the separation chamber atadjustable flow rates and, typically, are disposed at selected positionsalong the separation axis corresponding to discrete blood components. Toensure the extracted fluid exiting a selected extraction port issubstantially limited to a single phase, however, the phase boundariesbetween the separated blood components must be positioned along theseparation axis such that an extraction port contacts a single phase.For example, if the fraction containing white blood cells resides tooclose to the extraction port corresponding to platelet enriched plasma,white blood cells may enter the platelet enriched plasma stream exitingthe separation chamber, thereby degrading the extent of separationachieved during blood processing. Although conventional blood processingvia density centrifugation is capable of efficient separation ofindividual blood components, the purities of individual componentsobtained using this method is often not optimal for use in manytherapeutic applications.

As a result of the inability to achieve optimal purity levels usingcentrifugation separation alone, a number of complementary separationtechniques based on filtration, elutriation and affinity-basedtechniques have been developed to achieve the optimal purities neededfor use of blood components as therapeutic agents. These techniques,however, often reduce the overall yield realized and may reduce thetherapeutic efficacy of the blood components collected. Exemplarymethods and devices of blood processing via filtration, elutriation andaffinity based methods are described in U.S. Pat. No. 6,334,842.

Centrifugal blood component separation apparatus has been described incommonly assigned U.S. Pat. No. 7,605,388, for instance. As described inU.S. Pat. No. 7,605,388, an optical cell may be configured such thatwhite blood cells can be extracted through a first extraction port,plasma and/or platelets can be extracted through second extraction port,and red blood cells can be extracted through third extraction port. Asalso mentioned in U.S. Pat. No. 7,605,388 (but not shown), optical cellsof separation chambers can include one or more dams positioned proximateto the extraction ports to facilitate selective extraction of separatedblood components having reduced impurities arising from adjacentcomponents. The use of dams in blood processing via densitycentrifugation is known in the art and described in U.S. Pat. Nos.6,053,856; 6,334,842 and 6,514,189.

SUMMARY OF THE INVENTION

This invention provides methods, devices and device components forimproving the processing of fluids comprising fluid components, such asblood, components of blood and fluids derived from blood. Methods,devices and device components of the present invention are capable ofmonitoring and controlling separation of blood into discrete componentsand subsequent collection of selected components.

It has been found that certain transient conditions can cause loss ofcertain blood components, particularly white blood cells, in anoptically controlled blood separation apparatus. Improvements to anoptical chamber, wherein blood components are extracted from aseparation chamber, have been found to improve the efficiency of whiteblood cell collection.

A function of the centrifuge blood processing system described hereinmay be the collection of white blood cells. It has been found that thecollection of white blood cells is highly sensitive to changing flowconditions. If the pumps controlling fluid flow stop, the interfacebetween the red blood cells and the buffy coat generally falls, at leasttemporarily, to the level of the red blood cell extraction port. In suchcircumstances, a layer of white cells that had been collected on top ofthe red blood cell layer is frequently carried into the red blood cellextraction port and returned to the patient or donor. Since such whitecells are co-mingled with the total blood volume of the patient/donor,they are no longer available for collection without significantre-processing of the patient's blood. Such losses can significantlydecrease the efficiency of white blood cell collection.

According to the present invention, the optical cell of the separationvessel comprises at least a buffy coat extraction port and a red bloodcell extraction port. White cells collect at the buffy coat extractionport. A ramp, a dam and a shield direct white blood cells towards thebuffy coat extraction port. The shield leaves a small gap adjacent thebuffy coat extraction port. The red blood cell extraction port extendsinto the optical cell a sufficient radial distance from the axis ofrotation along a separation axis such that an orifice lies between thetop of the shield and the ramp, as measured radially from the axis ofrotation along a separation axis.

This configuration allows white cell-containing buffy coat to bewithdrawn from the optical cell through the buffy coat extraction portfor further separation in a fluidized-bed filtration chamber. If theflow conditions are interrupted, for example, by stopping one or more ofthe pumps, the RBC level falls to the level of the orifice of the RBCextraction port. The dam and ramp, however, prevent the buffy coat layerand white cells from flowing downstream to the third extraction port,thus preserving the white cells for collection when steady state flowconditions are re-established.

A further feature of the optical cell reduces false detection of redblood cells in the first extraction port, a condition that might cause aloss of collectable white cells. An extraction port comprised a steppedlumen having a larger diameter bore radially outwardly and a smallerdiameter bore radially inwardly. The larger diameter bore is needed toallow for a sufficiently large area for optical detection of conditionsin flux monitoring regions. The smaller diameter lumen is needed topromote a higher flow velocity through a white cell tube. The volume ofwhite cells collected is comparatively small, compared to the volumes ofred blood cells or plasma being processed through the system. A narrowlumen in the white cell tube reduces the possibility of stagnation inthe white cell line. Nevertheless, it is believed that vortices in thefluid flowing through the lumen in a prior art design may temporarilycapture white blood cells. White cells may continue to accumulate in thevicinity of a lip until a critical volume is dislodged and passesthrough the small diameter area of the lumen. The accumulation of whitecells near the flux monitoring regions impedes the transmission of lightthrough the flux monitoring regions. The darkening of these regions maybe erroneously interpreted as red blood cells. To alleviate thiscondition, a lumen or bore in the first extraction port has afrustroconical taper.

A feature of the present apparatus may comprise an optical cell for aseparation chamber of a density centrifuge blood processing system forseparating fluid components, the optical cell being adapted to bemounted on a rotor of said blood processing system, the optical cellcomprising an extraction chamber adapted to transmit at least a portionof an incident optical beam; a first extraction port extending radiallyoutwardly into said optical cell with respect to an axis of rotation ofthe rotor and being adapted to transmit at least a portion of theincident optical beam, the first extraction port having a bore forpassing fluid components and an orifice; a red blood cell extractionport downstream from said first extraction port with respect to fluidflowing through the optical cell and having an orifice extendingradially outwardly into the optical cell beyond the orifice of the firstextraction port; a dam between said first extraction port and said redblood cell extraction port, the dam being generally perpendicular tofluid flowing through said optical cell, and having an upper edge and alower edge, the lower edge being radially outward from the upper edge,wherein the orifice of the first extraction port and the orifice of thered cell extraction port are radially between the upper edge and thelower edge of the dam.

Another object of the invention may be to provide an optical cell with afluid passageway placed radially outward from a dam.

Yet another object of the invention may be to provide an optical cellwith a ramp at a lower edge of a dam, the ramp extending from the damupstream beyond a first extraction port. The ramp may extend outwardlyfrom a junction between the ramp and the dam. The ramp may besubstantially planar.

Another object or feature may be an optical cell having a plate adjacentan orifice of a first extraction port, the plate being spaced away fromthe orifice.

In another aspect of the apparatus, an optical cell may have a dam thatslants from an upstream position adjacent a wall of the optical cell toa downstream position adjacent a first extraction port.

Another aspect of the apparatus may comprise an extraction port having abore in fluid communication with an orifice of the extraction port, thebore having a first diameter, a lumen having a second diameter smallerthan said first diameter, and a frustro-conical passageway coupling thebore to the lumen.

These and other features and advantages of the invention will beapparent from the following description, drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing of a centrifuge blood separation apparatuswith an optical monitoring and control system.

FIG. 2 is a plan view of a blood component separation vessel and tubingset.

FIG. 3 is a section view of an optical cell of a separation chamber.

FIG. 4 is a perspective view of the optical cell of FIG. 3.

FIG. 5 is an illustration of an observation area, showing a part of theoptical cell of FIG. 3.

FIG. 6 shows a schematic of an exemplary control system capable ofcontrolling blood processing.

FIG. 7 is a perspective view of an optical cell of the present inventionwith an outer wall removed.

FIG. 8 is a plan view of the optical cell of FIG. 7.

FIG. 9 is a sectional view of the optical cell taken along line 9-9 ofFIG. 8. The outer wall is shown in section.

FIG. 10 is a sectional view of the optical cell taken along line 10-10of FIG. 8.

FIG. 11 is a sectional view of the optical cell taken along line 11-11of FIG. 8.

DETAILED DESCRIPTION OF THE INVENTION

Referring to the drawings, like numerals indicate like elements and thesame number appearing in more than one drawing refers to the sameelement. In addition, hereinafter, the following definitions apply:

The terms “light” and “electromagnetic radiation” are used synonymously.Light useful for the present invention includes gamma rays, X-rays,ultraviolet light, visible light, infrared light, microwaves, radiowaves or any combination of these. “Separation axis” refers to the axisalong which blood components having different densities are separated ina density centrifuge. As a separation chamber is rotated about a centralrotation axis in a density centrifuge, the centrifugal force is directedalong separation axes. Accordingly, a plurality of axes rotates aboutthe central rotation axis of a density centrifuge.

FIG. 1 schematically illustrates an exemplary embodiment of a bloodcomponent separation device 10 with an optical monitoring system capableof measuring a light intensities corresponding to patterns of lightoriginating from an observation region on a separation chamber. Theillustrated separation device 10 comprises light source 12, lightcollection element 14, and two-dimensional detector 16. Light source 12is in optical communication with a density centrifuge 18 comprising aseparation chamber 20 which rotates about central rotation axis 22.Rotation about central rotation axis 22 results in separation of a bloodsample in the separation chamber into discrete blood components along aplurality of rotating separation axes oriented orthogonal to the centralrotation axis 22. In a preferred embodiment, separation chamber 20 isheld in an internal, circular groove in a rotor 24 wherein theseparation chamber 20 is positioned and fastened. During operation ofthe density centrifuge, the rotor is operationally connected to arotating means such that both rotor and separation chamber are rotatedabout the central rotation axis 22. In the schematic shown in FIG. 1,the blood sample is separated into an outer higher density phasecorresponding to a red blood cell component, an intermediate densityphase corresponding to a white blood cell and platelet-containingcomponent (e.g. buffy coat) and a lower density inner phasecorresponding to a platelet enriched plasma component.

Light source 12 provides incident light beam 26, which illuminates anobservation region 28 on separation chamber 20. In one embodiment, lightsource 12 is capable of generating an incident light beam, a portion ofwhich is transmitted through at least one blood component undergoingseparation in separation chamber 20. At least a portion of scattered ortransmitted light 28 from the observation region 28 is collected bylight collection element 14. Light collection element 14 is capable ofdirecting at least a portion of the collected light 28 ontotwo-dimensional detector 16, e.g., a digital camera. The two-dimensionaldetector 16 detects patterns of scattered and/or transmitted light 28from the observation region. In an exemplary embodiment, two-dimensionaldistributions of light intensities comprise images corresponding topatterns of light originating from the observation region 28. In oneembodiment, images of the present invention are monochrome images, whichprovide a measurement of the brightness of separated blood componentsalong the separation axis. Alternatively, images of the presentinvention are color images, which provide a measurement of the colors ofseparated blood components along the separation axis.

Observation region 28 is positioned on a portion of the densitycentrifuge 18, preferably on the separation chamber 20. In the exemplaryembodiment illustrated in FIG. 1, separated blood components and phaseboundaries between optically differentiable blood components areviewable in observation region 28. In one embodiment, the observationregion is positioned on an optical cell of the separation chamber havingwindows for transmitting the incident beam through the blood sampleundergoing processing. In an alternative preferred embodiment, one ormore extraction ports (not shown in FIG. 1) are viewable in observationregion 28. In another embodiment, observation region 28 is positioned onthe top of the separation chamber 20 such that leaks of the blood sampleand/or improper alignment of the separation chamber or filler areviewable. In another alternative embodiment, the observation region 28is positioned on a portion of the separation chamber such that thecomposition of a separated blood component can be directly monitored.For example, a monitoring system of the present invention provides amethod of characterizing the type of cellular component collected andcounting the amount of cells extracted from the separation chamber as afunction of time. Alternatively, the monitoring system is arranged suchthat the concentration of non-cellular blood components, such as bloodplasma proteins, is directly measured. In one embodiment, theobservation region 28 is arranged such that a plurality of measurementsare obtained from every measured two-dimensional distribution ofscattered and/or transmitted light intensities.

Optionally, the observation region 28 can also be illuminated by lightsource 30, which is positioned on the same side of the separationchamber as the light collection element and two-dimensional detector.Light source 30 is positioned such that it generates an incident beam 32which is scattered by the blood sample and/or centrifuge. A portion ofthe light from light source 30 scattered by the separation chamber andis collected by light collection element 14 and detected by detector 16.The detector 16 is also capable of generating output signalscorresponding to light intensities or images. In the exemplaryembodiment shown in FIG. 1, two-dimensional detector 16 is operationallyconnected to a centrifugation device controller 34 capable of receivingthe output signals. The device controller 34 displays the measuredintensity distributions, stores the measured intensity distributions,processes measured intensity distributions in real time, transmitscontrol signals to various optical and mechanical components of themonitoring system and centrifuge or any combination of these. The devicecontroller 34 is operationally connected to centrifuge 18 and is capableof adjusting selected operating conditions of the centrifuge, such asthe flow rates of cellular and non-cellular components out of theseparation chamber, the position of one or more phase boundaries alongthe separation axes, rotational velocity of the separation chamber aboutcentral rotation axis 22, the infusion of anticoagulation agents orother blood processing agents to the blood sample, or any combination ofthese.

As shown in FIG. 1, the controller 34 can also be operationallyconnected to light source 12 or epi-illumination light source 30. Inthis embodiment, the device controller 34 and/or detector 16 are capableof generating output signals for controlling illumination conditions.For example, output signals from a detector can be used to control thetiming of illumination pulses, illumination intensities, thedistribution of illumination wavelengths, or the position of lightsource 10 or of the epi-illumination light source 30. As also shown inthe embodiment illustrated in FIG. 1, centrifugation device controllerand two-dimensional detector are in two way communication. In thisembodiment, the device controller sends control signals to the detector16 to selectively adjust detector exposure time, detector gain and toswitch between monochrome and color imaging.

The separation chamber 20 and an associated blood component bag andtubing set 40 are illustrated in FIG. 2. The bag and tubing set 40 isintended for single-use, that is, the separation chamber and tubing setare disposable after use with a single donor. The pre-connectedextracorporeal tubing set 40 may include a cassette assembly 42 and anumber of tubing/collection assemblies 44, 46, 48, 50, 52, and 54interconnected therewith. Preferably, a blood removal/return tubingassembly 44 provides a single needle interface between a donor and theremainder of the tubing set 40 (although a two-needle set-up may also beused, not shown). At least two lines 56, 58 are provided in assembly 44for removal of blood from and return of components to the donor. Thisembodiment includes a cassette assembly 42, which is interconnectedbetween the tubing assembly 44, which connects the donor thereto, andblood inlet/blood component outlet tubing line sub-assembly 46, whichprovides the interface between cassette assembly 42 and blood processingseparation vessel 20. Four tubing lines 60, 62, 64 and 66 are shown inFIG. 2 for transport of blood and components to and from the processingvessel 12. An anticoagulant tubing assembly 48, a vent bag tubing linesub-assembly 50, a red blood cell collection assembly 52, and a whiteblood cell assembly 54 are also interconnected with cassette assembly 42in this embodiment. As will be appreciated, the extracorporeal tubingcircuit or set 40 and blood processing vessel 20 are preferablypre-interconnected to yield a closed, pre-sterilized disposable assemblyfor a single use.

Emanating from vessel 20 is an RBC outlet tubing line 62 of the bloodinlet/blood component tubing assembly 46 which is interconnected throughpassageways of cassette 54 assembly 42 with RBC return tubing loop 68 toreturn separated RBCs to a donor or collection. For return, the RBCreturn tubing loop 68 is preferably inter-connected to the top of ablood return reservoir 70 of the cassette assembly 42. For collection,an RBC collection tubing assembly 52 is provided. RBC collectionassembly 52 preferably includes RBC collector tubing line 71 whichcommunicates with one or more RBC collection reservoirs or bags 72, andair removal bags 74. Blood filters 76 may also be provided to removeresidual blood components, such as white cells.

In a portion of the cassette assembly 42, plasma tubing 64 of bloodinlet/blood component tubing assembly 46 interconnects with apump-engaging, plasma tubing loop 78 and a plasma return tubing loop 80.If collection of plasma is desired, a plasma collect bag (not shown) mayalso be provided. The plasma return tubing loop 80 returns plasma todonor/patient. For such purpose, the plasma return tubing loop 80 isinterconnected to the top of the blood return reservoir 70 of thecassette assembly 42. One or more types of uncollected blood components,e.g., red blood cells, plasma or platelets, collectively referred to asreturn blood components, will cyclically accumulate in and be removedfrom reservoir 70 during use.

Like the other separated blood components such as plasma or red bloodcells, white blood cells, the principal blood component collected in thepresent configuration, flow out of the separation chamber 20 through anoptical cell 90, which will be more particularly described below. Whiteblood cells are accumulated in a filtration chamber 82 and areperiodically emptied into white cell tube 66. At appropriate intervals,the white cells are pumped through a pump loop 84 and a tubing line 86to a white cell collection bag 88. Alternatively, excess blood componentcould be returned to the donor through loop 92, which is coupled to theblood return reservoir 70.

The cassette assembly 42 in the embodiment of FIG. 2, may be mountedupon and operatively interface with a pump/valve/sensor assembly of theblood component separation device 10 during use. Further details of anapheresis system set-up including the loading and interaction of adisposable assembly 40 with a blood component separation device 10, maybe found in U.S. Pat. No. 5,653,887; No. 5,676,644; No. 5,702,357; No.5,720,716; No. 5,722,946; No. 5,738,644; No. 5,750,025; No. 5,795,317;No. 5,837,150; No. 5,919,154; No. 5,921,950; No. 5,941,842; and No.6,129,656, inter alia, and are not exhaustively repeated here.

FIG. 3 is a top plan view of a prior art optical cell 90 of a separationchamber as described in U.S. Pat. No. 7,605,388. The device 10 of FIG. 1acts to produce an observation area 100 that captures images of theoptical cell 90 as the optical cell passes under the light collectionelement 14. Visible in observation area 100 is a first calibrationmarker comprising an edge 102 of the optical cell and a secondcalibration marker 104 comprising a series of bars 1 mm in thickness andhaving a known absorption and scattering characteristics. First andsecond calibration markers provide references for optimizing focusing ofthe light collection element, indicating the positions and physicaldimensions of portions of a phase boundary monitoring region andmeasuring the positions of phase boundaries between the red blood cellcontaining component, the buffy layer and the plasma component.

FIG. 4 provides a perspective view of an optical cell 90 for monitoringblood processing via density centrifugation, as described in U.S. Pat.No. 7,605,388. The present invention comprises improvements to such anoptical cell. The illustrated prior-art optical cell 90 comprises ablood component extraction chamber 160, a first extraction port 162, asecond extraction port 164 and a third extraction port 166. Extractionchamber 160 comprises a first side wall 168 and a second side wall 170which define a blood separation region 172, wherein blood components areseparated along separation axis 174 on the basis of density uponformation of a centrifugal field by a density centrifuge. In theembodiment shown in FIG. 4, extraction chamber 160, first extractionport 162 and second extraction port 164, are each capable of passing atleast a portion of light scattered by blood or blood components in bloodseparation region 172, first extraction port 162, or second extractionport 164. Blood components of different densities are extracted throughdifferent extraction ports because first, second and third extractionports 162, 164 and 166 are in fluid communication with different regionsof blood separation region 172 during blood processing.

As described in U.S. Pat. No. 7,605,388, optical cell 90 is configuredsuch that white blood cells can be extracted through first extractionport 162, plasma and/or platelets can be extracted through secondextraction port 164, and red blood cells can be extracted through thirdextraction port 166. As also mentioned in U.S. Pat. No. 7,605,388,optical cells of separation chambers can include one or more darnspositioned proximate to the extraction ports to facilitate selectiveextraction of separated blood components having reduced impuritiesarising from adjacent components. As mentioned above, the use of dams inblood processing via density centrifugation is known in the art anddescribed in U.S. Pat. Nos. 6,053,856; 6,334,842 and 6,514,189.

FIG. 5 shows the observation region 100 focused on the optical cell 90of the separation chamber 20. The image in FIG. 5 includes a phaseboundary monitoring region 106 and a white blood cell extraction portmonitoring region 108 of the optical cell. Visible in phase boundarymonitoring region 106 are a red blood cell containing component 110, aplasma component 112 and a mixed phase buffy coat layer 114 having bothwhite blood cells and platelets. The edge 102 of the optical cellcomprises a first calibration marker for determining the absoluteposition of phase boundaries between optically differentiable bloodcomponents. The second calibration marker 104 is useful for optimizingthe focusing of the light collection element and indicating thepositions and physical dimensions of a phase boundary region 106 andwhite blood cell extraction port monitoring region 108. White blood cellextraction port monitoring region 108 includes a first flux monitoringregion 116 and a second flux monitoring region 118 positioned on whiteblood cell extraction port 119 of the optical cell. In this example fromU.S. Pat. No. 7,605,308, extraction port 119 has an orifice 121configured to collect white blood cells in the human blood sample andextends a distance along the separation axis such that it terminatesproximate to the buffy coat layer in the rotating separation chamber.

The intensity of light transmitted through the first and second fluxmonitoring regions 116 and 118 depends on the concentration, spatialdistribution, and cell-type of cellular material exiting the separationchamber. Light intensities transmitted through first and second fluxmonitoring regions 116 and 118 are acquired as a function of time andanalyzed to characterize the composition and flux of cellular materialout of the separation chamber. As cellular material, such as white bloodcells and red blood cells, absorbs and scatters light from the lightsources, passage of cellular material through the extraction port wasobserved to decrease the observed transmitted light intensities.

FIG. 6 shows a schematic of a process control system for the bloodprocessing device 10. The exemplary control system 120 illustrated inFIG. 6 comprises master

Procedure Control system 122 in two way communication with a dataacquisition and analysis system 124. Master Procedure Control system 122is capable of receiving input signals corresponding to a selected bloodprocessing procedure, a sample undergoing processing, or a patientundergoing treatment. Based on these input signals, Procedure ControlSystem 122 generates and transmits procedure requests and procedurecommands 126 to the smart slave data acquisition and analysis system124. The master Procedure Control system 122 also generates andtransmits a series of test commands 128 to smart slave data acquisitionand analysis system 124. Data acquisition and analysis system 124 iscapable of receiving test commands 128 and generating test responsesignals 130 which verify that the control system 120 is fully functionaland that the patient or blood sample identified by the data acquisitionand analysis system 124 is correctly associated with the selected bloodprocessing procedure or therapy.

The data acquisition and analysis system 124 comprises a first computerprocessor 132 in two-way communication with a second computer processor134. First computer processor 132 is configured to receive procedurerequests and procedure commands 126 from master Procedure Control system122 and transmit processing commands 136 to second computer processor134. Second computer processor 134 analyzes the processing commands 136and transmits camera setting commands 138 to the CCD camera and lightcollection element 16 which provide information related to establishingthe proper exposure time, camera and light collection element position,field of view, color or monochrome imaging and other parametersnecessary for acquiring high quality images of the blood processingdevice. First computer processor 132 is also configured to transmitillumination control and triggering commands 140 to light source andcamera triggering hardware 142. Using centrifuge positional encoderdata, the triggering hardware 142 transmits electronic trigger signalsto the light source driver circuits 144 and camera trigger 146. Camera16 measures light intensities comprising images of the observationregion 100 on the blood processing device. The raw image data istransmitted to the second computer processor 134 for image formattingand real time image processing. In a density centrifuge, an image isacquired upon every second rotation of the separation chamber. For arotational velocity of 3000 rotations per minute, this corresponds toacquisition of an image every 40 milliseconds.

The formatted image data is operated on by second computer processor 134using one or more image-processing algorithms, which extractmeasurements from the image data and determine information aboutphysical and chemical characteristics of the blood components undergoingprocessing and the operation of the blood processing device itself.

Immediately after creation of a new image data object, it is placed ontoa linked list of image data objects designated as the image data list148. This list stores image data information backwards in time. For anacquisition rate of 25 frames per second, 25 image data objects areinserted onto the image data list every second. The image data list actsas a managed circular buffer by deleting the oldest image data off thetail end of the list while inserting newly acquired image date at thehead of the list.

Image data objects in the image data list are periodically examined bythe first computer processor 132 and provide key data sets formonitoring and controlling blood processing. Measurements generated fromthe operation of the image-data analysis algorithms establish the basisof image information output signals 150 sent to the master ProcedureControl system 122 and also serve as the basis of output signals sent tothe camera 16, light sources, and camera triggering hardware 142 tooptimize the quality of the images acquired an analyzed.

Centrifugation device controllers are capable of selective adjustment ofthe position of one or more phase boundaries along the separation axes.For example, centrifugation device controllers may adjust the positionof phase boundaries by varying the flow rates of one or more selectedblood components out of the separation chamber. This can be achievedthrough the use of pumps, such as peristaltic pumps, to effectuatemovement through tubing. Inlet pumps can be provided which are capableof forcing material out of the separation chamber. The centrifugationdevice controller is capable of shutting down the centrifuge uponreceiving signals indicating a leak of blood components out of theseparation chamber, a misalignment of the separation chamber, a clot inthe extraction ports or similar condition. The centrifuge controller iscapable of regulating the infusion of a blood agent, such as ananti-coagulating agent, to the blood sample undergoing processing.Alternatively, the centrifugation device controller comprises a meansfor controlling the pumping rate of material out of the separationchamber in a manner capable of blowing out clots in the extractionports. For example, upon receiving an image indicating a platelet clotin a plasma extraction port, a centrifuge device controller is capableof automatically clearing the clot by lowering the red blood cell levelby reducing the pumping rate of the plasma pump and then rapidlyaccelerating the pumping rate of the plasma pump to force the clot outof the extraction port. Alternatively, the centrifuge controller iscapable of selectively adjusting the rotational velocity of thecentrifuge.

Improved Optical Cell

Although the centrifuge controller and optical system can be effectivein controlling the operation of a centrifuge blood processing system, asdescribed above, it has been found that certain transient conditions cancause loss of certain blood components, particularly white blood cells.Improvements to the optical cell 90, as described above have been foundto improve the efficiency of white blood cell collection.

A function of the centrifuge blood processing system described hereinmay be the collection of white blood cells. It may be desired, forexample, to collect white blood cells of a patient undergoingchemotherapy for cancer, so that the patient's own white blood cells canbe re-infused into the patient after a chemotherapy session. White cellscomprise a relatively small part of whole blood and are intermediate indensity between plasma and red blood cells. The optically controlledblood processing system collects white cells by controlling the locationof interfaces between plasma, buffy coat (which contains white cells andplatelets), and plasma such that the buffy coat can be removed from theseparation vessel 20 through the first extraction port 162 for furtherprocessing in the filtration chamber 82. In the prior art, the openingof the third (red blood cell) extraction port 166 was generally placednear the outer wall of the optical chamber, so as to be deep within thered cell layer. Such a configuration is very effective for thecollection of red blood cells. It has been found, however, that thecollection of white blood cells is highly sensitive to changing flowconditions. That is, if the Procedure Control System 122 stops the pumpscontrolling fluid flow (see above for exemplary reasons for stopping thepumps), it has been found that the interface between the red blood cellsand the buffy coat generally falls, at least temporarily, to the levelof the red blood cell extraction port. In such circumstances, a layer ofwhite cells that had been collected on top of the red blood cell layeris frequently carried into the red blood cell extraction port andreturned to the patient or donor. Since such white cells are co-mingledwith the total blood volume of the patient/donor, they are no longeravailable for collection without significant re-processing of thepatient's blood. Such losses can significantly decrease the efficiencyof white blood cell collection.

An optical cell 180 for improved white cell extraction is illustrated inFIGS. 7 through 11. The optical cell 180 comprises a first or buffy coatextraction port 182, a second or plasma extraction port 184, and a thirdor red blood cell extraction port 186. When mounted on the rotor of acentrifuge blood separation device, the extraction ports extend radiallyinwardly toward the axis of rotation of the rotor. Upstream from theextraction ports, a curved surface 188 forms a nozzle that acceleratesblood components passing through the separation chamber 20 towards theextraction ports. Downstream from the curved surface 188, white cellscollect above (that is, closer to the axis of rotation) the layer of redblood cells. A ramp 190, a dam 192 and a shield 194 direct white bloodcells towards the first extraction port 182. The ramp 190 is a generallyplanar sheet that rises gradually towards axis of rotation, lifting theRBC layer and the white cell-containing buffy coat as the bloodcomponents approach the first extraction port. The dam 192 intersectsthe ramp 190 and slants downstream towards the extraction port. Theaction of blood components flowing around the separation bag 20 directthe white cells towards the first extraction port 182. The shield 194comprises two walls 196, 198 that connect with each other and the ramp190, the dam 192 and a bottom wall 202 of the optical cell 180. A plate200 caps the two walls 196, 198 and faces the first extraction port 182,leaving a small gap 204 between the plate 200 and the first extractionport 182.

The third or red blood cell extraction port 186 extends into the opticalcell 180 a sufficient radial distance from the axis of rotation along aseparation axis such that an orifice 206 lies between the plate 200 andthe ramp 190, as measured radially from the axis of rotation along aseparation axis. The third extraction port 186 is spacedcircumferentially downstream from the first extraction port 182.

The optical cell 180 has a lip 201 that faces radially outwardly whenthe separation vessel 20 is mounted in the rotor of the blood separator.The lip 201 is sealed to a flexible outer wall 203 of the separationvessel. Under the influence of centrifugal forces created by the rotor,the outer wall 203 conforms to the shape of a groove in the rotor,thereby creating a space between the ramp 190 and the wall 203.Concentrated red blood cells pass beneath the ramp 190 and accumulatebehind the ramp 190, dam 192, and shield 194, where the red blood cellscan be extracted through the red blood cell extraction port 186.

This configuration allows white cell-containing buffy coat to bewithdrawn from the optical cell through the first extraction port forfurther separation in the filtration chamber 82. If the flow conditionsare interrupted, for example, by stopping one or more of the pumps, theRBC level falls to the level of the orifice 206 of the RBC extractionport 186. The dam and ramp, however, prevent the buffy coat layer andwhite cells from flowing downstream to the third extraction port, thuspreserving the white cells for collection when steady state flowconditions are re-established.

A further feature of the optical cell 180 reduces false detection of redblood cells in the first extraction port 182, a condition that wouldcause the Procedure Control System 122 to pause the pumps, which mightcause a loss of collectable white cells. As shown in FIG. 3, the priorart first extraction port 162 comprised a stepped lumen 208 having alarger diameter bore radially outwardly and a smaller diameter boreradially inwardly, with a lip 210 between the two areas. The largerdiameter bore radially outward is needed to allow for a sufficientlylarge area for optical detection of conditions in the flux monitoringregions 116, 118. The smaller diameter radially inward is needed topromote a higher flow velocity through the white cell tube 66. Thevolume of white cells collected is comparatively small, compared to thevolumes of red blood cells or plasma being processed through the system.A narrow lumen in the white cell tube 66 reduces the possibility ofstagnation in the white cell line. Nevertheless, it is believed thatvortices in the fluid flowing through the lumen 208 in the prior artdesign of FIG. 3 may temporarily capture white blood cells or cellularaggregates. White cells may continue to accumulate in the vicinity ofthe lip until a critical volume is dislodged and passes through thesmall diameter area of the lumen. The accumulation of white cells nearthe flux monitoring regions 116, 118, impedes the transmission of lightthrough the flux monitoring regions. The darkening of these regions maybe erroneously interpreted by the Procedure Control System 122 as redblood cells. Corrective action by the Procedure Control System mayinterrupt the collection of white cells or may cause the pumps to bepaused needlessly. To alleviate this condition, a lumen or bore 212 inthe first extraction port 182 (see FIG. 11) has a frustroconical taper214 from a first downstream region 216 having a first diameter toward asecond upstream region 218 having a second diameter as defined by thelumen of the white cell tube 66.

The improved separation chamber 20 and optical cell 180 thus providemore efficient collection of white cells by reducing false detection ofred blood cells and associated changes in flow conditions and bypreventing white cell loss when flow conditions are changed.

1. An optical cell for a separation chamber of a density centrifugeblood processing system for separating fluid components, said opticalcell being adapted to be mounted on a rotor of said blood processingsystem, said optical cell comprising: an extraction chamber adapted totransmit at least a portion of an incident optical beam; a firstextraction port extending radially outwardly into said optical cell withrespect to an axis of rotation of said rotor and being adapted totransmit at least a portion of the incident optical beam, said firstextraction port having a bore for passing fluid components and anorifice; a red blood cell extraction port downstream from said firstextraction port with respect to fluid flowing through said optical celland having an orifice extending radially outwardly into said opticalcell beyond said orifice of said first extraction port; a dam betweensaid first extraction port and said red blood cell extraction port, saiddam being generally perpendicular to fluid flowing through said opticalcell, and having an upper edge and a lower edge, said lower edge beingradially outward from said upper edge, wherein said orifice of saidfirst extraction port and said orifice of said red cell extraction portare radially between said upper edge and said lower edge of said dam. 2.The optical cell of claim 1 further comprising a fluid passagewayradially outward from said dam.
 3. The optical cell of claim 1 furthercomprising a ramp at said lower edge of said dam, said a ramp extendingfrom said dam upstream beyond said first extraction port.
 4. The opticalcell of claim 3 wherein said ramp extends outwardly from a junctionbetween said ramp and said dam.
 5. The optical cell of claim 4 whereinsaid ramp is substantially planar.
 6. The optical cell of claim 3further comprising a fluid passageway radially outward from said ramp.7. The optical cell of claim 3 further comprising a plate adjacent saidorifice of said first extraction port, said plate being spaced away fromsaid orifice of said first extraction port.
 8. The optical cell of claim1 wherein said dam slants from an upstream position adjacent a wall ofsaid optical cell to a downstream position adjacent said firstextraction port.
 9. The optical cell of claim 1 wherein said firstextraction port further comprises a bore in fluid communication withsaid orifice of said first extraction port, said bore having a firstdiameter, a lumen in fluid communication with said bore, said lumenhaving a second diameter smaller than said first diameter, and afrustro-conical passageway coupling said bore to said lumen.
 10. Anoptical cell for a separation chamber of a density centrifuge bloodprocessing system for separating fluid components, said optical cellbeing adapted to be mounted on a rotor of said blood processing system,said optical cell comprising: an extraction chamber adapted to transmitat least a portion of an incident optical beam; and a first extractionport extending radially outwardly into said optical cell with respect toan axis of rotation of said rotor and being adapted to transmit at leasta portion of the incident optical beam, said first extraction porthaving a bore for passing fluid components and an orifice, said borebeing in fluid communication with said orifice of said first extractionport, said bore having a first diameter, a lumen in fluid communicationwith said bore, said lumen having a second diameter smaller than saidfirst diameter, and a frustro-conical passageway coupling said bore tosaid lumen.
 11. A tubing set for a density centrifuge blood processingsystem for separating fluid components, said tubing set comprising aseparation chamber adapted to be mounted on a rotor of said bloodprocessing system, an optical cell in fluid communication with saidseparation chamber, said optical cell comprising: an extraction chamberadapted to transmit at least a portion of an incident optical beam; afirst extraction port extending radially outwardly into said opticalcell with respect to an axis of rotation of said rotor and being adaptedto transmit at least a portion of the incident optical beam, said firstextraction port having a bore for passing fluid components and anorifice; a red blood cell extraction port downstream from said firstextraction port with respect to fluid flowing through said optical celland having an orifice extending radially outwardly into said opticalcell beyond said orifice of said first extraction port; a dam betweensaid first extraction port and said red blood cell extraction port, saiddam being generally perpendicular to fluid flowing through said opticalcell, and having an upper edge and a lower edge, said lower edge beingradially outward from said upper edge, wherein said orifice of saidfirst extraction port and said orifice of said red cell extraction portare radially between said upper edge and said lower edge of said dam.12. The tubing set of claim 11 wherein said optical cell furthercomprises a fluid passageway radially outward from said dam.
 13. Thetubing set of claim 11 further comprising a ramp at said lower edge ofsaid dam, said a ramp extending from said dam upstream beyond said firstextraction port.
 14. The tubing set of claim 13 wherein said rampextends outwardly from a junction between said ramp and said dam. 15.The tubing set of claim 14 wherein said ramp is substantially planar.16. The tubing set of claim 13 further comprising a fluid passagewayradially outward from said ramp.
 17. The tubing set of claim 13 furthercomprising a plate adjacent said orifice of said first extraction port,said plate being spaced away from said orifice of said first extractionport.
 18. The tubing set of claim 11 wherein said dam slants from anupstream position adjacent a wall of said optical cell to a downstreamposition adjacent said first extraction port.
 19. The tubing set 1 ofclaim 11 wherein said first extraction port further comprises a bore influid communication with said orifice of said first extraction port,said bore having a first diameter, a lumen in fluid communication withsaid bore, said lumen having a second diameter smaller than said firstdiameter, and a frustro-conical passageway coupling said bore to saidlumen.
 20. A tubing set for a density centrifuge blood processing systemfor separating fluid components, said tubing set comprising a separationchamber adapted to be mounted on a rotor of said blood processingsystem, an optical cell in fluid communication with said separationchamber, said optical cell comprising: an extraction chamber adapted totransmit at least a portion of an incident optical beam; and a firstextraction port extending radially outwardly into said optical cell withrespect to an axis of rotation of said rotor and being adapted totransmit at least a portion of the incident optical beam, said firstextraction port having a bore for passing fluid components and anorifice, said bore being in fluid communication with said orifice ofsaid first extraction port, said bore having a first diameter, a lumenin fluid communication with said bore, said lumen having a seconddiameter smaller than said first diameter, and a frustro-conicalpassageway coupling said bore to said lumen.
 21. A centrifugal bloodseparation system comprising a rotor adapted to impart centrifugal forceto separate blood into blood components, a light source adapted toselectively illuminate an observation region on said rotor, an opticalsensor adapted to detect light from said light source, a control systemin electrical communication with said rotor, said light source and saidoptical sensor and adapted to control said rotor, light source andsensor, a separation vessel mounted on said rotor, wherein blood may beseparated into blood components, an optical cell in fluid communicationwith said separation vessel, said optical cell comprising: an extractionchamber adapted to transmit at least a portion of an incident opticalbeam; a first extraction port extending radially outwardly into saidoptical cell with respect to an axis of rotation of said rotor and beingadapted to transmit at least a portion of the incident optical beam,said first extraction port having a bore for passing fluid componentsand an orifice; a red blood cell extraction port downstream from saidfirst extraction port with respect to fluid flowing through said opticalcell and having an orifice extending radially outwardly into saidoptical cell beyond said orifice of said first extraction port; a dambetween said first extraction port and said red blood cell extractionport, said dam being generally perpendicular to fluid flowing throughsaid optical cell, and having an upper edge and a lower edge, said loweredge being radially outward from said upper edge, wherein said orificeof said first extraction port and said orifice of said red cellextraction port are radially between said upper edge and said lower edgeof said dam.
 22. The centrifugal blood separation system of claim 21further comprising a fluid passageway radially outward from said dam.23. The centrifugal blood separation system of claim 21 furthercomprising a ramp at said lower edge of said dam, said a ramp extendingfrom said dam upstream beyond said first extraction port.
 24. Thecentrifugal blood separation system of claim 23 wherein said rampextends outwardly from a junction between said ramp and said dam. 25.The centrifugal blood separation system of claim 24 wherein said ramp issubstantially planar.
 26. The centrifugal blood separation system ofclaim 23 further comprising a fluid passageway radially outward fromsaid ramp.
 27. The centrifugal blood separation system of claim 23further comprising a plate adjacent said orifice of said firstextraction port, said plate being spaced away from said orifice of saidfirst extraction port.
 28. The centrifugal blood separation system ofclaim 21 wherein said dam slants from an upstream position adjacent awall of said optical cell to a downstream position adjacent said firstextraction port.
 29. The centrifugal blood separation system of claim 21wherein said first extraction port further comprises a bore in fluidcommunication with said orifice of said first extraction port, said borehaving a first diameter, a lumen in fluid communication with said bore,said lumen having a second diameter smaller than said first diameter,and a frustro-conical passageway coupling said bore to said lumen.
 30. Acentrifugal blood separation system comprising a rotor adapted to impartcentrifugal force to separate blood into blood components, a lightsource adapted to selectively illuminate an observation region on saidrotor, an optical sensor adapted to detect light from said light source,a control system in electrical communication with said rotor, said lightsource and said optical sensor and adapted to control said rotor, lightsource and sensor, a separation vessel mounted on said rotor, whereinblood may be separated into blood components, an optical cell in fluidcommunication with said separation vessel, said optical cell comprising:an extraction chamber adapted to transmit at least a portion of anincident optical beam; and a first extraction port extending radiallyoutwardly into said optical cell with respect to an axis of rotation ofsaid rotor and being adapted to transmit at least a portion of theincident optical beam, said first extraction port having a bore forpassing fluid components and an orifice, said bore being in fluidcommunication with said orifice of said first extraction port, said borehaving a first diameter, a lumen in fluid communication with said bore,said lumen having a second diameter smaller than said first diameter,and a frustro-conical passageway coupling said bore to said lumen.
 31. Amethod for controlling a centrifugal blood separation system comprisinga rotor adapted to impart centrifugal force to separate blood into bloodcomponents, said method comprising flowing blood into a separationchamber, said separation chamber having an extraction chamber, saidextraction chamber adapted to transmit at least a portion of an incidentoptical beam and having a first extraction port extending radiallyoutwardly into said extraction chamber with respect to an axis ofrotation of said rotor and being adapted to transmit at least a portionof the incident optical beam, said first extraction port having a borefor passing fluid components and an orifice, and a red blood cellextraction port downstream from said first extraction port with respectto fluid flowing through said extraction chamber and having an orificeextending radially outwardly into said extraction chamber beyond saidorifice of said first extraction port detecting fluid in an extractionchamber on said rotor with an optical control system comprising anoptical sensor and control system in communication with said rotor,controlling said rotor, said sensor and at least one pump on said bloodseparation system for controlling fluid flow in said blood separationsystem, and controlling fluid flow in said extraction chamber with amechanical control system whenever an interface between red blood cellsand a buffy coat layer to the level of said red blood cell extractionport.
 32. The method of claim 31 further comprising providing a dambetween said first extraction port and said red blood cell extractionport, said dam being generally perpendicular to fluid flowing throughsaid optical cell, and having an upper edge and a lower edge, said loweredge being radially outward from said upper edge, wherein an orifice ofsaid first extraction port and an orifice of said red cell extractionport are radially between said upper edge and said lower edge of saiddam.
 33. The method of claim 32 further comprising flowing fluidradially outward from said dam.
 34. The method of claim 33 furthercomprising flowing fluid radially outwardly from a ramp at said loweredge of said dam, said a ramp extending from said dam upstream beyondsaid first extraction port.